The Safety of Agalsidase Alfa Enzyme Replacement Therapy in Canadian Patients with Fabry Disease Following Implementation of a Bioreactor Process
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVE: Fabry disease, an X-linked lysosomal storage disorder characterized by absent or reduced alpha-galactosidase activity, is a lifelong disease that impairs patients' quality of life. Patients with Fabry disease have a considerably shortened lifespan, with mortality being mainly due to renal failure, cardiovascular disease, or cerebrovascular disease. Enzyme replacement therapy with agalsidase alfa has been shown to attenuate the renal, cardiovascular, and neuropathic disease progression associated with Fabry disease. The objective of this study was to investigate the safety of a new animal component-free version of agalsidase alfa. METHODS: A phase III/IV, open-label, single-arm, multicenter safety study was conducted in Canadian patients with Fabry disease between August 2011 and September 2017 as a regulatory requirement to assess the safety of agalsidase alfa produced using an animal component-free bioreactor process. Eligible patients had a documented diagnosis of Fabry disease and satisfied current Canadian guidelines for receiving enzyme replacement therapy for Fabry disease. Following treatment with animal component-free bioreactor-processed agalsidase alfa, treatment-emergent adverse events were monitored, and post hoc analyses of infusion-related reactions by antidrug antibody and neutralizing antibody statuses were conducted. The data were analyzed using descriptive statistics. RESULTS: A total of 167 patients (mean [standard deviation] age, 48.9 [14.8] years), including six pediatric patients (< 18 years of age), received at least one full or partial infusion of agalsidase alfa animal component-free. Fewer than 5% of treatment-emergent adverse events (212/4446) observed in 40 patients were reported as infusion-related reactions. Antidrug antibody and neutralizing antibody status did not affect the proportion of patients with infusion-related reactions. No clinically significant changes in vital signs were observed in patients over the course of the study. CONCLUSIONS: Long-term treatment with bioreactor-produced agalsidase alfa animal component-free did not reveal new safety signals in this population of Canadian patients with Fabry disease. The treatment-emergent adverse event profile was consistent with the clinical manifestations of the disease and the known safety profile of roller bottle-produced agalsidase alfa. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01298141.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".